Ultraviolet radiation and neurodegeneration: molecular mechanisms underlying dual neuroprotective and neurotoxic effects.

Ultraviolet radiation exhibits a complex, often contradictory link to neurodegeneration risk/progression, spanning clinically diagnosed diseases [Parkinson's Disease (PD), Alzheimer's Disease (AD), Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS)] or intermediate phenotypes (decreased neurogenesis, loss of hippocampal volume). The aim of this review is to highlight the dual impact of UV radiation by collecting and synthesizing experimental (preclinical and translational) evidence as well as epidemiological evidence. Current literature exhibits a clear dichotomy: while Vitamin D is capable of exerting a potent neuroprotective effect via anti-oxidant and anti-inflammatory pathways, chronic and intense UV radiation exposure actually hastens the progression or even drives neurodegeneration via a variety of mechanisms. UV radiation exerts its effects through various interconnected pathways: DNA damage pathways, ROS mediated pathways, vitamin D signaling and the skin-brain axis, which unifies both protective and degenerative effects of UV radiation. Owing to the increasing occurrence of neurodegenerative diseases in the general population, these pathways and mechanisms must be leveraged in future research to develop novel therapeutic and preventive strategies. Investigation of biomarkers linked to certain genetic and environmental factors that could provide a link to predisposition toward neurodegeneration and standardization of UV radiation dosimetry (exposure dose/duration) across experimental or pre-clinical studies must also be prioritized.